Appropriateness of early breast cancer management in relation to patient and hospital characteristics: a population based study in Northern Italy.

Administrative data may provide valuable information for monitoring the quality of care at population level and offer an efficient way of gathering data on individual patterns of care, and also to shed light on inequalities in access to appropriate medical care. The aim of the study was to investigate the role of patient and hospital characteristics in the initial treatment of early breast cancer using administrative data. Incident breast cancer patients were identified from hospital discharge records and linked to the radiotherapy outpatient database during 2000-2004 in the Piedmont region of Northwestern Italy. Women treated with breast-conserving surgery followed by radiotherapy (BCS + RT) were compared to those treated with BCS without radiotherapy (BCS w/o RT) or mastectomy using multinomial logistic regression models. Out of 16,022 incident cases, 46.2% received BCS + RT, 20.3% received BCS w/o RT, and 33.5% received a mastectomy. Compared to BCS + RT, the factors associated with BCS w/o RT were: increased age (OR = 1.54; 95% CI = 1.29-1.85, for ages 70-79 vs. <50), being unmarried (1.24; 1.13-1.36), presence of co-morbidities (1.32; 1.10-1.58), being treated at hospitals with low surgical volume (1.31; 1.07-1.60 for hospitals with less than 50 vs. > or =150 interventions/year), and living far from radiotherapy facilities (1.75; 1.39-2.20 for those at a distance of >45 min). These same factors were also associated with mastectomy. During the 5-year period observed, there was a trend of reduced probability of receiving a mastectomy (0.70; 0.56-0.88 for 2004 vs. 2000). The presence or absence of nodal involvement was positively associated with mastectomy (2.28; 1.83-2.85) and negatively associated with BCS w/o RT (0.65; 0.56-0.76). After adjustment for potential confounders, education level did not show any association with the type of treatment. Social and geographical factors, in addition to hospital specialization, should be considered to reduce inappropriateness of care for breast cancer.

Multidimensional geriatric assessment in treatment decision in elderly cancer patients: 6-year experience in an outpatient geriatric oncology service.

This prospective cohort study of consecutive elderly cancer patients was undertaken to evaluate the role of the multidimensional geriatric assessment (MGA) as an aid in treatment decision-making. A total of 571 cancer patients (aged > or =70) were enrolled during 6-year (1999-2005). All underwent MGA as part of the first evaluation. In multivariate analysis, the probability of receiving active, instead of palliative, treatment was negatively associated with increasing age (odds ratio=0.69 every 5 years, p=0.005), living alone (OR=0.54, p=0.031), dependence in activities of daily living (ADL score >0, OR=0.41, p=0.003) and a low body-mass index (BMI) (OR=0.51, p=0.061); while a positive association emerged for instrumental activities of daily living (IADL) score (OR=1.12 per point, p=0.019). Our data suggest that MGA, in addition to age, is a useful tool in clinical practice for deciding cancer treatment in elderly patients, with a major independent role played by living alone, ADL, IADL and BMI.

Opinions concerning euthanasia, life-sustaining treatment and acceleration of death: results of an Italian Association of Medical Oncology (AIOM) survey.

BACKGROUND: Advance directives, acceleration of death, euthanasia and 'life-sustaining treatment' have sparked much heated debate among the media, the public, doctors and political leaders. We evaluate the personal opinions of Italian Association of Medical Oncology (AIOM) members. PATIENTS AND METHODS: A 30-item questionnaire was developed and delivered to all 1,832 AIOM members. RESULTS: Six-hundred and eighty-five (37%) oncologists completed and returned the questionnaires. Sixty-three per cent felt culturally and psychologically prepared to face these issues. Fifty-four per cent believed that what had been decided while the patient enjoyed good health is no longer applicable in an advanced state of terminal illness. Thirty-nine per cent believed that doctors should abide by these directives, while 49% believed that this should be discussed on a case-by-case basis. Fourteen per cent of oncologists were favourable towards euthanasia and 42% only in particular circumstances. Fifty-six per cent had received at least one request for accelerating death: 15% consented, 50% discussed it with the patient and 31% refused. CONCLUSION: Advance directives, euthanasia, accelerated death and life-sustaining treatment represent considerable challenges for Italian oncologists. Although prepared to face these issues, AIOM members ask for a debate within the medical world and for a shared judicial regulation.

Induction chemotherapy followed by concurrent chemoradiotherapy in advanced head and neck squamous cell carcinoma.

BACKGROUND: A phase II study was carried out to investigate an induction regimen with cisplatin, paclitaxel followed by radiotherapy concurrent with weekly cisplatin for locally advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Stage III-IV disease patients were eligible. Two cisplatin (100 mg/m2) and paclitaxel (175 mg/m2) courses were administered every 21 days followed by standard fractionated external beam radiotherapy (approximately 70 Gy), concomitant to weekly cisplatin (30 mg/m2). RESULTS: Thirty-five patients were enrolled: over 70% had unresectable disease with bulky lesions. Grade 3-4 neutropenia developed in 14% and G3 mucositis in 23%. Locoregional control was achieved in 51%. Median time to progression and overall survival were 10,7 and 17 months respectively; 2- and 3-year survival rates were 30% and 25% respectively. CONCLUSION: Our induction two-drug regimen followed by chemoradiotherapy with concurrent weekly cisplatin was well tolerated with low acute toxicity and good locoregional control and survival rate.

Randomized study of vinorelbine--gemcitabine versus vinorelbine--carboplatin in patients with advanced non-small cell lung cancer.

PURPOSE: The objective of this trial was to compare two vinorelbine-based doublets with carboplatin (CBDCA-VC) or with gemcitabine (VG) in patients with stage IIIB-IV non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 316 patients with advanced NSCLC previously untreated were randomized to either vinorelbine 30 mg/m(2) D1,8 with carboplatin AUC 5 D1 (VC) or vinorelbine 25mg/m(2) with gemcitabine (VG) 1000 mg/m(2) both given D1,8 every 3 weeks. The primary endpoint was response rate with secondary parameters being survival (OS), progression-free survival (PFS), tolerance and clinical benefit. RESULTS: The median number of cycles was four in each arm with a total of 1268 cycles. The objective response (OR) on intent-to-treat was 20.8% in VC and 28% in VG (p=0.15). Median PFS was 3.9 months in VC and 4.4 months (mo) in VG (p=0.18). Median survival was significantly longer (p=0.01) for VG with 11.5 mo compared to 8.6 mo in VC with 1 year survival at 48.9 and 34.4%, respectively. Tolerance was better in the VG arm as compared to the VC patients. Four toxic deaths were recorded in the VC group. Clinical benefit response rate was 32.4% compared to 40.9% in 111 and 110 evaluable patients in VC and VG, respectively. CONCLUSION: VG compared to VC resulted in a similar overall response rate, favourable median survival and a better toxicity profile. For non-cisplatin-based chemotherapy, VG is a useful alternative.

Weekly cisplatin paclitaxel and continuous infusion fluorouracil in patients with recurrent and/or metastatic head and neck squamous cell carcinoma: a phase II study.

BACKGROUND: Cisplatin, paclitaxel and 5-fluorouracil (5-FU) have demonstrated significant activity in patients with advanced squamous head and neck cancer (HNSCC) despite relevant toxicity. A weekly administration of cisplatin and paclitaxel with continuous infusion of 5-FU could offer a better toxicity profile without affecting dose intensity or treatment outcome. We evaluated the toxicity and the activity of weekly cisplatin/paclitaxel with continuous infusion 5-FU in patients with recurrent and/or metastatic HNSCC. METHODS: A total of 44 patients were studied. Treatment consisted of two 6-week cycles with weekly cisplatin 20 mg/m2 and paclitaxel 60 mg/m2 and daily continuous infusion 5-FU 200 mg/m2 from day 1 to 42. Patients were evaluated for toxicity and response. RESULTS: 40 out of 44 patients were evaluable for response. After two cycles we observed seven complete responses (16%) and 12 partial responses (27%), with a 43% (95% CI 28-58%) overall response rate. Stable disease was seen in 13 patients (29%) and progressive disease in 12 patients (27%). Toxicity was mild in treated patients: we observed less than 10% of grade 3/4 hematological and gastroenteric toxicity. CONCLUSIONS: A weekly schedule of cisplatin and paclitaxel associated with continuous infusion 5-FU showed low toxicity in the treatment of advanced HNSCC while significant activity was conserved.

Phase II study of divided-dose vinblastine in advanced breast cancer patients.

The pharmacokinetics of a 5-day, continuous infusion of vinblastine have been reproduced by an i.v. divided bolus at 0 and 48 h [10]; this schedule can be easily applied to outpatients. We treated 26 evaluable patients with refractory, advanced breast cancer with 3.5-4 mg/m2 vinblastine given i.v. by a divided bolus at 0 and 48 h of 21-day cycles. Neurotoxicity and myelosuppression were the main side effects: severe constipation and peripheral neurotoxicity developed in 14% and 3% of the patients, respectively; severe leukopenia and thrombocytopenia occurred in 24% and 10% of the patients, respectively. One partial response, 14 no changes, and 11 progressions were obtained. Our results do not support the use of vinblastine in divided doses in treating this disease.

Paclitaxel administration on days 1 and 8 every 21 days in anthracycline-pretreated metastatic breast cancer patients. A multicenter phase II trial.

Paclitaxel is now included in second- and even first-line regimens in advanced breast cancer. The optimal dose and schedule of this drug, however, still remain a matter of investigation. A group of 57 consecutive patients with advanced breast cancer previously treated with anthracycline-containing regimens were submitted to treatment with single-agent paclitaxel administered at 130 mg/m2 on days 1 and 8 every 21 days. Of the 57 patients, 56 were fully evaluable, and of these 25 had an absolute anthracycline resistance, 14 a relative resistance and 17 were potentially sensitive. The median age of the patients was 57 years (range 33-71 years), their median performance status was 1 (0-3), and 27 (47%) had liver involvement, 17 (30%) lung involvement, 30 (53%) bone involvement and 15 (26%) skin/lymph node involvement. Toxicity was recorded in 295 cycles. This scheme was well tolerated, the dose-limiting toxicities being hematological and neurological. Grade 3/4 leukopenia was observed in 20% of patients at nadir, while grade 3 leukopenia was observed in 3% of patients at recycle. Only one patient experienced febrile neutropenia. Grade 2/3 neurotoxicity was observed in 26% of patients, leading to drug withdrawal in three. The treatment was given on an outpatient basis in all patients and the median relative dose intensity of 86.6 mg/m2 per week was 100% of the planned dose (range 75-100%). Three patients (5%) attained a complete clinical response and 12 (21%) a partial response for an overall response rate of 26% (95% confidence interval 18-38%), while 30 (53%) attained disease stabilization and 11 progressed (19%). Time to progression in responding patients was 10.3 months, and the median overall survival of the entire population was 15.4 months. To conclude, paclitaxel administration on days 1 and 8 every 21 days was active and manageable in advanced breast cancer patients previously treated with anthracyclines. The response obtained was durable.

Low dose adriamycin and ifosfamide in the treatment of advanced adult soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas are infrequent tumors (up to 1% of all neoplasms) in adult patients. Treatment of advanced disease is largely unsatisfactory. Only a few drugs are active agents and combination regimens offer limited and short-lived activity. High dose chemotherapy may be administered only to limited groups of patients. PATIENTS AND METHODS: We evaluated, in a phase II study, the adriamycin and ifosfamide combination regimen. The drugs were administered at 60 mg/sqm and 6 g/sqm dosage, respectively. The total number of treated patients was 42 of which 40 were evaluable. RESULTS: We observed 6 complete responses (14% response rate) and 6 partial responses (14%). The mean survival was 6 months (median 7.6 months). Toxicity was limited and reversible. CONCLUSION: While high dose chemotherapy may be reserved for selected groups of patients, an adriamycin and ifosfamide combination regimen at conventional doses can be administered to the great majority of patients with suboptimal performance status or with advanced age.

Osteoblastic flare assessed by serum alkaline phosphatase activity is an index of short duration of response in prostate cancer patients with bone metastases submitted to systemic therapy.Gruppo Onco Urologico Piemontese (G.O.U.P).

A transient rise in serum alkaline phosphatase (ALP) activity (ALP flare) after androgen deprivation in prostate cancer patients with bone metastases has been previously correlated with both response to therapy and poor prognosis. In the present study we analyzed data coming from an Italian multicenter phase III, trial aimed to compare the efficacy of treatment with goserelin alone with that of goserelin plus mitomycin C. Sixty-seven bone metastatic patients were enrolled: 32 were treated with goserelin and 35 with and goserelin plus mitomycin. 58 cases had ALP measured every month; and were considered for flare assessment. Remarkably elevated ALP and PSA levels at baseline were significantly correlated with poor prognosis. The addition of mitomycin to goserelin resulted in a greater percent reduction of PSA values with respect to goserelin alone but did not augment the time to progression and overall survival. The monthly profile of ALP serum levels was superimposable in patients assigned to hormone therapy or chemotherapy plus hormone therapy. Patients showing a flare in ALP activity (transient rise > 15% in ALP values with respect to baseline at the first month) were classified as responders to therapy or as having stable disease upon PSA evaluation and/or at bone pain assessment, but had a shorter time to progression (median 12 months) in comparison to those showing a different ALP pattern (median 23 months). The measurement of flare in ALP activity during androgen suppression with or without concomitant mitomycin administration, may permit the early identification of patients who are likely to progress rapidly, and hence be candidate for more aggressive treatments.

Combination chemotherapy with carboplatin and methotrexate in the treatment of advanced urothelial carcinoma. A phase II study.

The activity and toxicity of a carboplatin (300 mg/m2, day 1) and methotrexate (50 mg/m2, days 8 and 15) combination chemotherapy in the treatment of advanced urothelial cancer (UC) was evaluated in the present study. A total of 49 patients entered the study: 44 patients were evaluable for response, and 48 for toxicity. A complete response (CR) was found in 4/44 patients (9.1%) and a partial remission (PR) in 12/44 patients (27.2%) for an overall response rate of 16/44 (36.3%). Stable disease was found in 21/44 patients (47.7%), and progressive disease in 7/44 patients (15.9%). Survival was significantly longer in responding patients than nonresponders (median: 62 weeks vs 50 weeks, P < .05). Hematologic and renal toxicities were mild, thrombocytopenia and leukopenia being the most relevant side effects. The first consecutive 7 patients received methotrexate also on day 22; 5 of them underwent grade III-IV hematologic toxicity, so methotrexate on day 22 was omitted in the subsequent patients. No toxic deaths were reported. CBDCA and MTX combination chemotherapy is well tolerated and moderately active in the treatment of advanced urothelial cancer and may represent a valid alternative to cisplatin-containing regimens in patients with poor performance status and/or impaired renal function.

Phase II trial of weekly 4-epi-doxorubicin (epirubicin) in squamous cell carcinoma of the head and neck.

We tested 4'-epi-doxorubicin (epirubicin) in 15 patients with advanced squamous cell carcinoma of the head and neck which progressed after conventional therapy. The drug was administered at the dosage of 25 mg/m2 weekly. No patient achieved objective response. Toxicity was minimal. Epirubicin given at this dose and schedule revealed no activity in heavily pretreated patients with cancer of the head and neck.

Antiemetic activity of oral lorazepam in addition to methylprednisolone and metoclopramide in the prophylactic treatment of vomiting induced by cisplatin. A double-blind, placebo-controlled study with crossover design.

AIMS AND BACKGROUND: It has been suggested that lorazepam has a definite role as an antiemetic drug in antiemetic cocktails. In this study we examined the antiemetic efficacy of metoclopramide (200 mg) and methylprednisolone (1000 mg) with or without lorazepam. METHODS: Sixty patients treated with cisplatin-containing regimens were entered into a randomized, double-blind study with cross-over. Lorazepam 2.5 mg or placebo were administered orally the evening before therapy and just after the beginning of fluid infusion for chemotherapy. Degree of nausea and number of vomiting episodes, together with somnolence, were recorded on a data flow sheet and visual-analogue scales. RESULTS: 100 cycles (50 patients) are evaluable. In 39 cycles there was no nausea and vomiting, in 74 cycles acceptable control of emesis was reached (0-2 episodes of vomiting), without significant differences among the two arms. However, nausea was shorter in lorazepam arm (p < 0.01), and 80% of the patients preferred treatment with lorazepam (p < 0.003). Anxiety was reduced in the patients treated with lorazepam (p < 0.4). CONCLUSIONS: Lorazepam improves tolerability to cisplatin-containing chemotherapy, mainly by influencing the psychological status of the patient and favoring the amnestic process.

Comparison of methylprednisolone and metoclopramide in the prophylactic treatment of cis-platin-induced nausea and vomiting.

Sixty-one patients undergoing treatment with cis-platin-containing regimens were given prophylactically either metoclopramide or methylprednisolone, in order to reduce the gastrointestinal side effects. Vomiting occurred in 79% of the cycles (128/162), and had a distressing intensity in 39.5% of cycles (64/162). No significant differences were observed between metoclopramide and methylprednisolone with respect to number and duration of vomiting episodes and duration of nausea and anorexia. Two of 6 patients benefited from substitution of metoclopramide for methylprednisolone; only 1/11 benefited from the substitution of methylprednisolone for metoclopramide. Metoclopramide and methylprednisolone, at the dosage and schedule used, were well tolerated and moderately active in preventing nausea and vomiting induced by cis-platin; their use in combination could further improve these results.

The role of induction chemotherapy in inoperable ovarian cancer.

Thirty patients with bulky advanced ovarian cancer surgically not resectable, received combination chemotherapy (median of 4.1 cycles; range, 3-7) including cisplatin or carboplatin, followed by a second surgical effort. Clinical CR + PR was observed in 24/30 (80%) patients after chemotherapy. Our study deals only with these 24 patients, and the 6 patients who did not respond to chemotherapy are not part of this report. At debulking, 7/24 (29.1%) patients had a complete macroscopic resection; 9/24 (37.5%) patients had a partial resection (residual tumor less than 2 cm). These data suggest that debulking is feasible and successful after chemotherapy containing cisplatin or its derivative. Overall median survival from diagnosis was 18.9 months; the 3-year survival rate was 28%. Median progression-free survival from diagnosis was 13.5 months. The results observed in our study indicate that the use of induction chemotherapy can play an important role in increasing the chances of optimal debulking in patients presenting with unresectable ovarian cancer.

Randomized comparison of goserelin acetate versus mitomycin C plus goserelin acetate in previously untreated prostate cancer patients with bone metastases.

In a prospective trial conducted by the Gruppo Onco Urologico Piemontese, newly diagnosed prostate cancer patients with bone metastases were randomized to receive goserelin (3.6 mg subcutaneously every 4 weeks) or goserelin plus mitomycin at 14 mg/m2 i.v. every 6 weeks. Treatment was planned to be continued until progression. The study was interrupted because of inadequate accrual rate when 63 patients had been recruited. A long-term follow-up (median, 47 months), performed to counterbalance the limited number of patients included, revealed no difference in time to progression and overall survival between the study treatments. However, 56.5% of assessable patients allocated to the chemotherapy arm presented a > or =90% reduction of prostate-specific antigen levels compared with 36.3% in the goserelin group, and previously elevated levels normalized in 73.9% versus 45.4%. Non-progressing patients received 5-7 cycles of mitomycin C with acceptable toxicity, but the cytotoxic treatment was interrupted early in all cases within the first year due to cumulative myelotoxicity. In conclusion, the results, although inconclusive, fail to support a clear advantage in terms of cost/benefit of chemotherapy plus hormone therapy over hormone treatment alone in advanced prostate cancer with bone involvement.

Vinorelbine treatment of recurrent salivary gland carcinomas.

Twenty patients (13 males, 7 females, median age 61 years, range 27-74) with recurrent adenocarcinoma-like tumors of major (10 patients) and minor (10 patients) salivary gland origin (13 adenoid cystic carcinoma, 5 adenocarcinoma, 1 malignant mixed tumor, 1 undifferentiated carcinoma) were treated with vinorelbine at the dose of 30 mg/m2 i.v. weekly. Sixteen patients had been previously treated with surgery + radiation, 3 with surgery + radiotherapy + Novantrone and 1 with radiotherapy alone. Nine patients had local recurrence, 2 local relapse + metastasis and 9 metastasis alone. Site of metastases are: lung (7), bone (1), lung + bone (2), lung + bone + lymph-node + skin (1). Overall 174 courses were given (median 9, range 6-19). Responses were: PR in 4 patients (20%) with a median duration of 6 months (3-9), 9 NC (45%) with a median duration of 3.5 months and 7 PD (35%). The median survival time was 10 months for PR/NC patients, 4 months for non-responders. Median overall survival was 7 months. Vinorelbine has a moderate activity in these very advanced cases.

[Treatment of N2-3 pulmonary carcinoma. Preoperative radio-chemotherapy]. / Trattamento del carcinoma polmonare N2-3. Radio-chemioterapia preoperatoria.

Preoperative integrated neo-adjuvant radio-chemotherapy was performed in 8 patients suffering from NSCLC bronchial carcinoma at stages IIIA-IIIB (N3 mediastinal). After treatment, 7 patients underwent apparently radical pulmonary exeresis, whereas the patient with adenocarcinoma (T2 N2 M0) was not operated due to the recurrence of disease following supraclavicular lymph node metastasis. Preoperative radio-chemotherapy allows the sub-staging of the disease and the insertion of these patients into the operating programme.

[Long-term survival following chemotherapy for recurrent head and neck cancer: patient characteristics]. / Caratteristiche dei lungo sopravviventi dopo chemioterapia nelle recidive dei carcinomi dela testa e del collo.

Eighty-one patients with recurrent squamous cell carcinoma of the head and neck (60 patients) or undifferentiated carcinoma of the nasopharyngeal type (21 patients) were treated with cisplatin (80-100 mg/m2iv d1) and 5-fluorouracil (750-1000 mg/m2Cl d1-5). In squamous cell carcinoma patients there were 7 complete responses (11.6%), 25 partial responses (41.7%), 20 stable disease situations (33.3%) and 8 progressions (13.3%). In nasopharyngeal carcinoma patients there were 6 complete responses (28.6%), 9 partial responses (42.8%), 3 stable disease situations (14.3%) and 3 progression (14.3%). There were 5/60 patients (8.3%) with disease-free survival > 18 months in the squamous cell carcinoma group and 2/21 (9%) in the nasopharyngeal carcinoma group. All long-term survival patients had the following characteristics: good performance status (0-1 ECOG scale), disease- free interval from the first treatment > 12 months, local non-bulky relapse (rT1-2). A re-irradiation with palliative doses (20-48 Gy) was conducted in 3/7 patients. This treatment may have improved the response to drugs with regard to length and quality.